guia para diagnostico de vih

8/10/2019 Guia para diagnostico de VIH

1/109

GUIDELINES

FOR

MANAGEMENT OF

OPPORTUNISTIC INFECTIONS

AND

ANTI RETROVIRAL TREATMENT

IN ADOLESCENTS AND ADULTS

IN ETHIOPIA

Federal HIV/AIDS Prevention and Control Office

Federal Ministry of HealthMarch 2008


2/109

PART I

GUIDELINES

FOR

MANAGEMENT OF OPPORTUNISTIC

INFECTIONS IN ADULTS

AND ADOLESCENTS

ii


3/109

Table of Contents

Foreword iv

Acknowledgement vAcronyms and Abbreviations vi1. Introduction 12. Objectives and Targets 2

2.1. Objectives 2

2.2. Targets 2

3. Management of Common Opportunistic Infections 2

4. Unit 1: Management of OI of the Respiratory System 31.1 Bacterial pneumonia 6

1.2 Pneumonia due to Pneumocystis jiroveci. 6

1.3 Pulmonary tuberculosis 7

1.4 Correlation of pulmonary diseases and CD4 count

in HIV-infected patients 9Unit 2: Management of GI Opportunistic Diseases 11

2.1. Dysphagia and odynophagia 11

2.2. Diarrhoea 12

2.3 Peri-anal problems 14

2.4. Peri-anal and/or genital herpes 15

Unit 3: Management of Opportunistic Diseases of theNervous system 16

3.1. Peripheral neuropathies 17

3.2. Persistent headache with (+/-) neurological manifestations

(+/-) seizure 18

3.3. Management of common CNS infections presenting with

headache and/or seizure 193.3.1. Toxoplasmosis 19

3.3.2 Management of seizure associated with

toxoplasmosis and other CNS OIs 21

3.3.3 Cryptococcosis 23

3.3.4 CNS Tuberculosis 25

Unit 4: Management of Skin Disorders 264.1 Aetiological Classification of Skin Disorders in HIV disease. 27

4.2 Selected skin conditions in patients with HIV infection 28

4.2.1 Seborrheic dermatitis 28

4.2.2 Pruritic Papular Eruption 29

4.2.3 Kaposis Sarcoma 29

Unit 5: Management of Fever 305.1 Selected causes of fever in AIDS patients 33

5.1.1 Malaria 335.1.2 Visceral Leishmaniasis 33

5.1.3 Sepsis 34

Unit 6: Some Special Conditions in OI Management 356.1 Initiating ART in context of an acute OI 35

6.2 When to initiate ART in context of an acute OI 36

iii


4/109

Tables1. Summary for CD4 correlates with respiratory diseases 5

2. Summary of main respiratory infections 9

3. Diagnostic approach when a patient presents with respiratory

Symptoms and CD4 count is >200 cells/L or


5/109

Foreword

Antiretroviral treatment began in 2003 and free ART was launched in Ethiopia in 2005.

An estimated 977,394 Ethiopians are currently living with HIV, out of whom 258,264require antiretroviral treatment (ART).

Recognizing the urgent need for antiretroviral treatment, the Government of Ethiopia(GOE) issued the first antiretroviral (ARV) guidelines in 2003, which were revised in

2005 to facilitate a rapid scale up of ART. Within two years, patients on treatment at 117

hospitals and 108 health centres increased from 900 to 62,221.

Opportunistic infections (OIs) and malignancies resulting from depletion of the immune

system are major causes of morbidities and mortalities among AIDS patients. Prophylaxis

and early treatment of OIs have been clearly shown to prolong and improve the quality oflife for people living with HIV, even before the advent of ART.

In order to realise universal access to free ART by 2009/2010, the Federal Ministry ofHealth (MOH) is committed to decentralize further the expansion and integration of

HIV/AIDS prevention and control activities with primary health care services at grass

roots where the majority of the population lives.

Expansion and strengthening ART care and treatment activities at regional, zonal, woreda

and kebele levels through targeted social mobilization and active community

participation are planned to create an environment to prevent and control spread of theepidemic. The process of task shifting: training of nurses and community health agents in

prevention, treatment, care and support activities will further strengthen community

linkages and ensure availability of standard minimum packages of HIV/AIDS services at

primary health care level.

This revised 3rd

edition of guidelines for use of OI and ARV drugs in adult andadolescent care is based on recent national and worldwide evidence and experience and is

intended as a clear guide for rational and safe use of OI and antiretroviral drugs. The

Federal Ministry of Health believes that these guidelines, along with other nationalimplementation guidelines, will be instrumental in accelerating and scaling up ART

uptake and treatment and prevention of other opportunistic infections to meet the

millennium development goals (MDG).

Dr. Betru TekleDirector General

Federal HIV Prevention and Control Office

v


6/109

Acknowledgements

The Federal HIV/AIDS Prevention and Control Office (FHAPCO) is grateful to the

following individuals and institutions for their inputs in revising and developing theseguidelines.

Dr. Yibeltal Assefa HAPCODr. Altaye Habtegiorgis FHI

Dr. Sisaye Sirgu WHO

Dr. Hamza Adus I-TECH-Ethiopia

Dr. Yigeremu Abebe CHAIDr. Zenebe Melaku CU-ICAP

Dr. Jilalu Asmera I-TECH-Ethiopia

Dr. Berhanu Tekle JHU-TSEHAI

Dr. Endalk Gebrie JHU-TSEHAIDr. Solomon Ahmed CDC-Ethiopia

Dr. Beniam Feleke CDC-EthiopiaProfessor Sileshi Lulseged CDC-Ethiopia

Dr. Yoseph Mamo UCSD-Ethiopia

Dr. Teklu Belay I-TECH-Ethiopia

Dr. Mulugeta Workalemahu FHAPCOMrs. Pamela Scott PEPFAR Ethiopia

HAPCO also wishes to acknowledge the contributions of Regional Health Bureaus andRegional HAPCOs in the development of this guideline.

The printing of the Guidelines has been funded by the U.S. Presidents Emergency Planfor AIDS Relief (PEPFAR). The Federal HAPCO is grateful for the support.

vi


7/109

Acronyms and Abbreviations

AED Antiepileptic Drug

AFB Acid Fast BacilliART Antiretroviral Therapy

BF Blood FilmBID Twice per day

BP Blood PressureCBC Complete Blood CountCHF Congestive Heart failure

CHAI Clinton Foundation HIV/AIDS Initiative

CMV Cytomegalovirus

CNS Central Nervous SystemCPK Creatinine phospho Kinase

CSF Cerebro Spinal Fluid

CT Computerized Tomography

CTM CotrimoxazoleCX-ray Chest X-ray

D4T/DDI Stavudin/DidanosinDOT Directly Observed Treatment

EMG Electromyography

EMB Ethambutol

FHI Family Health InternationalGI Gastrointestinal

GIT Gastrointestinal Tract

GOE Government of EthiopiaHAART Highly Active AntiRetroviral Treatment

HAPCO HIV/AIDS Prevention and Control OfficeHCT HIV Counselling and TestingHEENT Head, Eyes, Ears, Nose and Throat

HSV Herpes Simplex Virus

Hx HistoryICP Isoniazid Chemoprophylaxis

IgG Immunoglobulin

IM Intramuscular

INH IsoniazidIRIS Immuno Reconstitution Inflammatory Syndrome

IPT Isoniazid Preventive Treatment

IV IntravenousKS Kaposi Sarcoma

LDH Lactate Dehydrogenase

LFT Liver Function TestLP Lumbar Puncture

LIP Lymphocytic Interstitial Pneumonia

MAC Mycobacterium avium complex

MDR Multidrug-resistant TB

vii


8/109

MRI Magnetic Resonance ImagingMTB Miliary Tuberculosis

NCS Nerve conduction studies

NNRTI None-Nucleoside Reverse Transcriptase InhibitorOI Opportunistic Infection

PCP Pneumocystis PneumoniaPCR Polymerase Chain ReactionPLWHA People Living With HIV/AIDS

PML Progressive Multifocal Leuckoencephalopathy

PMN: Polymorphonuclear leukocyte

PO By MouthPPV Positive Predictive Value

Px Physical examination

PZA PyrazinamideQID Four times per day

RBS Random Blood Sugar

RDT Rapid Diagnostic TestRFT Renal Function Test

Rx Treatment

STM Streptomycin

TB TuberculosisTBC Tuberculosis

TMP-SMX Trimethoprim Sulphamethoxazole

UTI Urinary Tract InfectionURTI Upper Respiratory Tract Infection

VL Viceral LeishmaniasisVZV Varicela Zoster Virus

WHO World Health Organisation

XDR-TB Extensively Drug-Resistant Tuberculosis2RHZE/6HE Rifampicin, Isoniazid, Pyrizinamide, Ethambutol

/Isoniazid, Ethambutol

viii


9/109


10/109

They are intended to complement more comprehensive textbooks, journals, andother relevant informational materials

They will require periodic updates based on local data and clinical experiences

2. Objectives and Targets

2.1. Objectives

To provide standardized simplified preventive (prophylaxis) and management

approaches to opportunistic infections common in Ethiopia

To promote evidence-based, safe and rational use of OI drugs

To demonstrate management of OI in the context of ART

To prepare a reference manual for health service providers, program managers, and

people living with HIV

2.2. Targets

Health care workers caring for people infected with HIV

HIV/AIDS program managers, health planners, and researchers

Institutions involved in OI drug procurement and supply chain management

3. Management of Common Opportunistic Infections

Opportunistic infections are the predominant causes of morbidity and mortality among

HIV-infected patients. Main areas affected are the nervous, gastro-intestinal and

respiratory systems, and the skin. The level of immunity determines the occurrence andtype of opportunistic infections. In general milder infections, such as herpes zoster and

other skin infections, occur early whereas serious life- threatening infections such as CNS

toxoplasmosis and cryptococcal meningitis occur later with severe immunity. Some life-

threatening infections, such as pneumonia and TB, may occur early as well as later.

When TB occurs later it is atypical, more disseminated and more extra pulmonary.

Although these guidelines are organised by systems, patients must be assessed and

managed holistically since HIV disease is a multi-systemic condition. Concurrentinfectious and non-infectious conditions, such as diabetes, hypertension and bronchial

asthma, sometimes occur with OIs, and require appropriate management. Non-

opportunistic pathogens such as M. Tuberculosis, Entamoeba histolytica or Strongyloidsstercoralis, etc are frequent, severe and recurrent among patients with HIV disease. All

patients with OI must be followed up after initiation of treatment; if there is no

improvement, patients may be referred for better care or more thorough investigation if

facilities permit. All patients must be enrolled in chronic HIV care services, including

ART, after standard clinical and immunological assessments of eligibility are conducted.

Treatment of OIs entails administration of different drugs, therefore drug interactions,

toxicities, and overlap toxicities should always be addressed, especially in patientsalready on ART and/or TB DOTS.

2


11/109

Unit 1: Management of OI of the Respiratory System .

Patients with HIV infection are vulnerable to respiratory diseases from early to advancedstages of AIDS. These can be infectious, neoplastic or related to problems outside the

lungs, with concurrent or pre-existing lung conditions like hypersensitivity or chronicobstructive lung disease. The approach to respiratory dysfunction in HIV patients should

be based on the same clinical considerations as for patients with normal immunity andconditions that occur during immune deficiency state.

The common respiratory diseases among people living with HIV are opportunistic

infections, which occur across the spectrum of clinical HIV infection: infection by

Streptococcus pneumoniae, Mycobacterium tuberculosis and Pneumocystis. jiroveci.Upper respiratory tract and lower respiratory tract infections are common but lower

respiratory tract infections are life-threatening. This unit presents basic principles in

diagnosis and treatment of the HIV-infected patient with respiratory disease. Emphasis is

given to common aetiologies, clinical presentations, recommended investigations andtreatment in resource-limited settings.

Management of patients with respiratory disease starts with taking a good history and

meticulous physical examination of the upper and lower respiratory tracts, complemented

by laboratory investigations, like sputum for gram stain and AFB, with chest X-ray in

selected patients.

Upper respiratory tract diseases include pharyngitis, tonsillitis, rhinitis, sinusitis andotitis media. They occur relatively early, before advanced immune deficiency developsand thus constitute WHO stage II clinical conditions. The common organisms are

Streptococcus pneumoniae, Staph aureus or H. influenza. Candida albicans is also arecognized cause of pharyngitis indicative of clinical stage III.

Diagnosis in Ethiopia is usually based on clinical examination only. In pharyngitis, thethroat looks inflamed with hypertrophy and exudates formation on the pharynx. Otitis

media presents with earache and headache associated with discharge from the external

ear. This condition is common in children but also often seen in adult patients with HIV

infection and hence PIHCT should be offered routinely. On examination there may betragus tenderness with visible ear discharge and/or evidence of inflamed tympanic

membranes on otoscope examination. Sinusitis produces facial pain and headache that is

associated with post nasal drip. Usually the maxillary sinus is involved and patients willhave tenderness over the cheeks and tender regional lymphadenopathy can be also

detected. Oral candidiasis presents with oral sores, change in the sense of taste, and when

it involves the throat and oesophagus, pain on swallowing; however it can beasymptomatic in some patients. Diagnosis is established clinically when a curd-like

membrane is visible on the surface of the tongue and buccal mucosa. Typically the base

of the membrane bleeds upon scraping it.

3


12/109

Treatment: the preferred regimen for bacterial URI is amoxicillin/clavulanic acid 625mgBID for seven to ten days. An alterative regimen is ampicillin or amoxicillin preferably

extending the course of treatment to fourteen days. If penicillin allergy is a problem,CTM 960mg bid can be given for the same period. Give paracetamol for pain. It is

necessary to document resolution of clinical findings after treatment and if not resolvedrefer to the next health facility. Oral and pharyngeal thrush are treated with oralmiconazole gel 2% applied twice daily; patients should not eat/drink for two hours after

applying the gel. If this does not work or is unavailable, use fluconazole 100mg daily for

14 days. This regimen is also effective for oro-pharyngeal candidiasis.

Common diseases of lower respiratory tract infections: include TB, bacterialpneumonia and PCP. The principal symptoms of respiratory diseases include cough,sputum production, chest pain, dyspnea, wheezing and haemoptysis but it is difficult to

differentiate these by history and physical examination alone. In any case, the history

should indicate whether onset of illness is acute or chronic and also record symptomsrelated to upper respiratory tract diseases like nasal discharge, sneezing, facial pain,

stridor and tracheal pain. Some of these symptoms may be primarily due to illnesses

outside the lungs, like congestive heart failure resulting from valve, myocardial and

pericardial diseases.

Physical Examination:

Assess vital signs, recording blood pressure, respiratory rate and temperature.

Observe for evidence of distress, such as inability to talk, facial sweating, nasalflaring, use of accessory muscles, presence of central cyanosis and altered mental

function. Presence of these signs indicates a need for consultation withexperienced doctors for possible inpatient management or referral to next health

facility.

By the end of the physical examination you should be able to formulate a differential

diagnosis to explain the anatomic abnormality.

It is useful to consider the following during patient assessment

Evidence of advanced immune deficiency state e.g. oral thrush etc.

Evidence for extra pulmonary involvement like meningitis, arthritis, hepatitis

and pericarditis. Presence of these conditions usually warrants inpatientmanagement.

Evidence for poor prognosis, like age over 60, severe distress manifested bytachypnea (RR>30/minute), cyanosis, grunting, retractions, multiple lobe

involvement and systolic blood pressure below 80mmHg. These conditionsnecessitate inpatient management.

If the CD4 count is available, it is useful to consider the aetiologicaldifferential diagnosis (refer to Table 1)

4


13/109

Table 1: Summary for CD4 correlates with respiratory diseasesCD4 count/L. Respiratory disease

Any CD4 count URI

Bacterial pneumonia

TB

Lymphoma

Non-specific interstitialpneumonias.

CD4 count


14/109

Bacterial pneumonia.

This can occur in immune-competent individuals but the risk increases six-fold amongHIV-infected individuals. Bacterial pneumonia occurs during the whole spectrum of HIV

disease, but tends to be more severe and recurrent as the CD4 counts drops significantly;in addition pneumonia can concomitantly present with sinusitis and/or bacteraemia. If nottreated promptly, extra pulmonary complications like empyema, meningitis, pericarditis,

hepatitis and arthritis can follow. Streptococcus pneumoniae and Haemophylusinfluenzae are the most common aetiologies of community acquired pneumonia.

Typically the patient presents with sudden onset of cough, sputum production, chest pain,fever and/or shortness of breath.

Diagnosis: The clinical suspicion is based on a history of acute symptoms presented overdays to a few weeks and/or abnormal physical signs of systemic infection and

consolidation in the affected lung/s. Gram stain of sputum is useful to confirm diagnosis

of pneumonia and possibly to predict the organism causing it. Chest X-ray can be usefulin diagnosis of bacterial pneumonia but can be non- specific in advanced immune

deficiency stage. Refer to algorithm.

Treatment: Amoxicillin is the drug of choice for community-acquired bacterialpneumonia. Start with 500mg tid for ten days. In patients with penicillin allergy use

erythromycin 500mg qid for the same duration. Follow up is necessary to document

resolution of initial symptoms or to monitor complications. Moreover, the patient has tobe staged to determine eligibility for ART. When the patient has presented with clinical

evidence of severe pneumonia, which includes tachypnea (RR>30/minute), old age (>70years), cyanosis, hypotension, systolic blood pressure


15/109

diagnosis of PCP is based on demonstration of the organism from an induced sputumsample using special stains like Giemsa or methylamine silver stains, but these tests are

not routinely done in Ethiopia.

Treatment: use Trimethoprim 15-25 mg/Kg, which amounts to cotrimoxazole 3- 4

single-strength tablets three or four times daily for 21 days. Close monitoring is necessaryduring the initial five days of treatment and if patient grows sicker, administration ofoxygen is useful. In severely ill patients with marked respiratory distress and extensive

chest X-ray findings, prednisolone has to be given simultaneously; 80mg for the first five

days, 40 mg until 11 days and 20 mg until completion of cotrimoxazole. Toxicity of

cotrimoxazole, like skin rash, bone marrow suppression, hepatitis and renal failure can betroublesome in some patients with advanced HIV disease and requires close monitoring.

Alternative regimens for mild to moderate cases of PCP include:

1. clindamycin 600 mg qid plus primaquine 15 mg bid

or

2. clindamycin 600 mg qid plus dapsone 100 mg daily.

Secondary prophylaxis after completion of the course of treatment withcotrimoxazole should be started (refer to national ART guideline). In addition, the

patient has to be prepared for ART as s/he is automatically eligible for ARTregardless of the CD4 count.

1.3. Pulmonary Tuberculosis.

M. tuberculosis is the leading cause of morbidity and mortality among PLWHA

worldwide. In Ethiopia the co-infection rate is 20-50% creating a dual epidemic of

symptomatic HIV infection and tuberculosis. Tuberculosis enhances progression ofHIV infection by inducing immune activation, and HIV increases the risk of infection

as well as reactivation of latent tuberculosis. Hence it is conceivable that tuberculosis

can occur across the clinical spectrum of HIV infection.

Tuberculosis can cause pulmonary and/or extra-pulmonary symptoms depending on

the degree of immune suppression. In patients with good immunity, tuberculosistypically involves the apical lung fields and causes either cavitations or fibrosis

visible in a chest X-ray. However, in patients with CD4 count below 200 cells/L,

tuberculosis is often atypical, with lower zone infiltration on chest X-ray and tends to

be extra-pulmonary; e.g. pleural effusion, scrofula, meningitis and other form oftuberculosis.

A TB suspect is a patient with persistent cough and/or sputum production of longerthan two weeks with constitutional symptoms including fever, weight loss and

anorexia. This mode of presentation indicates pulmonary tuberculosis, which is the

major form in both HIV positive and negative patients. Symptoms of extra pulmonarydisease are more common in patients with HIV co-infection particularly when the

CD4 count is low. Systemic symptoms like fever, sweating, weight loss and cough

7


16/109

are non-specific manifestations of many complications of HIV, but the health workershould consider tuberculosis as a first possibility. Offer HCT for all TB suspects and

refer co-infected individuals to HIV care and treatment.

Diagnosis: tuberculosis is likely when any of the following is detected singly or in

combination:1. Specific radiological findings on chest CX-ray, which include apicalfibrosis or cavity lesion.

2. Typical findings of epitheloid cells with caseous formation on cytological

or histological examination of tissue sample or bacteriologic tests, such as

smear and culture, from infected sample

Definitive diagnosis of tuberculosis is however based on isolation of Micobacterium

tuberculosis on culture media. This test is not widely available in Ethiopia and thereforeis seldom done. In most health facilities in Ethiopia pulmonary tuberculosis is diagnosed

when two sputum samples are positive for acid fast bacilli or one sample is positive for

AFB and the chest X-ray shows typical radiological features.

Tuberculosis can present as immune reconstitution syndrome followingcommencement of HAART. These patients need to be treated for tuberculosis and

continue taking ART, but drug toxicity and interactions should be monitored strictly;

refer to ART guideline.

Treatment: TB treatment has two phases: an intensive phase of 8 weeks followed bya continuation phase of 4-6 months, depending on the regimen used. Selection of the

regimen depends on the treatment category of the patient (refer to TB-leprosy manual

for details). A new TB patient co-infected with HIV belongs to category I andaccordingly the following drugs are used (refer to national TB manual for treatment

details for the remaining categories);

1. Intensive phase: rifampicin, isoniazid, ethambutol and pyrazinamide for 8 weeks.

Follow patients for clinical evidence of hepatitis. Bear in mind that drug

interactions of nevirapine with rifampin can occur and potential additive toxicityto the liver when ARVs are used with anti-TB drugs during this phase.

2. Continuation phase: INH with ethambutol for six months.

Atypical mycobacterium infections among HIV infected individuals are uncommon

in Ethiopia. In one study only two cases of MAC were reported among patients withpulmonary TB and HIV infection in Ethiopia.

This regimen is associated with high recurrence rate of active tuberculosis after completion of treatment.

Getachew etal.

8


17/109

Table 2: Summary of main respiratory infections

Aetiology Clinical Lab Characteristic 1stline drug/sfindings investigations Radiological`

changes

Bacterial

pneumonia

Fever,

productivecough, dyspnea

and tachypnea 200 cells/L or 200

andpossibility

CD4 2

weeks

Consider TB Consider

TB, PCP,

lymphoma

KS

Sputum AFB. Often difficult to differentiate

TB and PCP radio logically.

Decision has to be based on

clinical presentation and

sputum result for AFB. Kaposi

usually present with

concomitant mucosal dermal

lesions.

Cavitory Sputum production ,

hemoptysis

TB

Lung abscess

Nocardia

TB, lung

abscess

Nocardia

Sputum AFB.

Consider anti-

TB treatment.

TB is the common cause of

cavitations.

Miliary Patient is usually ill TB TB and

rarely fungal

infections.

Sputum AFB

Empirical

treatment

In most patients CD4 is very

low and watch for IRIS.

Nodular < 1 CM TB

Bacterial

pneumonia

TB

Bacterial

pneumonia

Sputum for

Gram stain or

AFB

Decide treatment based on the

clinical course.

>1cm TB TB,

lymphoma

Sputum AFB Tissue diagnosis is preferable;

decision to treat needs expert

opinion.

Diffuse/bilater

al

Acute onset in one

week

Consider

bacterial

pneumonia

Consider

bacterial

pneumonia

Sputum Gram

stain

Empiric

treatment forBP

Do not use cotrimoxazole to

treat bacterial pneumonia.

Sub acute onset

>2weeks

TB TB, PCP Sputum AFB

Treat for TB or

PCP based on

sputum result.

Concomitant infection with

TB and PCP is possible if

CD4 is below 200/L.

10


19/109

Unit 2: Management of Gastrointestinal Opportunistic Diseases

The GI OI diseases commonly manifest with diarrhoea, nausea and vomiting, dysphagiaand odynophagia among others. There are a number of opportunistic and pathogenic

organisms causing GI disease in patients infected with HIV.

A scenario of multiple concurrent GI infections is fairly common. The general principle

of managing GI opportunistic infections is identifying and treating the specific offending

agent providing supportive care to monitor situations such as fluid loss. A number ofdrugs can cause adverse effects that present with clinical manifestations referable to GIS.

The clinical presentations may be similar to manifestations of OIs of the GI, posing

challenges to successful differential diagnosis.

2.1. Dysphagia and odynophagia

Dysphagia (difficulty in swallowing) and odynophagia (painful swallowing) are

symptoms of oesphagitis occurring at advanced stages of AIDS. They are usually causedby candida, HSV, CMV, and aphthous ulcers. As well as a sign of severe

immunodeficiency, esophagitis also seriously impairs the patients nutritional status.

Therefore prompt diagnosis and treatment are mandatory to avert nutritionalcomplications among other things.

Diagnosis: is frequently made on clinical grounds, but when facilities are available upperGI endoscopy with or without biopsy may be done.

Treatment: Dysphagia and/or odynophagia are treated as oesophageal candida onclinical grounds, in particular when oropharyngeal candida is present. Thrush or

oropharyngeal candida is characterized by white, painless, plaque-like lesions on thebuccal surface and/or tongue. Patients are empirically treated with Fluconazole inpresumptive oesophageal candida. If the response is unsatisfactory they are referred or

investigated if facilities are available, to rule out other causes. Patients with dysphagia

and/or odynophagia appear to be in stage IV of HIV disease; therefore, the necessarybaseline assessment and counselling must be done in order to put them on ART.

Drug of choice: Fluconazole 200 mg PO daily for 14 daysAlternatively, ketoconazole 200 mg twice daily for 4 weeks.

Risk of recurrence after completing treatment may be high. Patients should be re-treated

and ART initiated after the appropriate workup, if patient is not already on ART. If the

patient is on ART, s/he should be investigated for treatment failure. Take necessaryprecautions regarding drug interactions especially with ketoconazole. Patients may need

hospital admission for supportive care till the oesophageal symptoms improve and

necessary long term treatments are started.

11


20/109

Diarrhoea

Diarrhoea is defined as passing more than four loose or watery stools/day for >3 days. Itmay be acute or chronic, persistent or intermittent. Diarrhoea is among the most frequent

symptoms of HIV disease. Delay in treatment can result in fluid loss and hemodynamicinstability. Chronic diarrhoea may also lead to nutritional deficiencies and wasting.Diarrhoea is caused by opportunistic or pathogenic organisms, such as viruses (including

HIV), bacteria, protozoa, fungi, helminthic, non-infectious causes and drugs. (Diarrhoea

occurs as an adverse reaction to a number of drugs).

Diagnosis: Investigate the duration, volume, frequency, consistency of stools as well asany history of abdominal pain, tenesmus, nausea, vomiting, and presence ofconstitutional symptoms such as fever. Thorough physical examination is necessary to

find out the state of hydration and the status of HIV disease among other things.

Laboratory evaluation: Stool microscopy including modified acid fast stainStool culture when indicated (optional)

Management: The most important first step is correction of fluid loss. Depending on theseverity of dehydration, ORS or IV fluid therapy can be given. Patients with severe

dehydration are admitted for intravenous fluid administration.

12


21/109

Table 4: Management of dehydration

Two of the following signs:

Lethargy or

unconscious

Sunken eyes

Not able to drink ordrinking poorly

Skin when pinched

goes back very

slowly

Systolic bloodpressure (SBP)


22/109

If specific enteric pathogen is identified or strongly suspected on clinical grounds, it

should be treated accordingly.

Table 5: Treatment of specific enteric pathogens

Agent CD4 Symptom Diagnosis Rx

E. hystolytica any bloody stool,

colitis

Stool

microscopy

Metronidazole

Giardia any Watery diarrhoea Stoolmicroscopy

Metronidazole

Cryptosporidium


23/109

Treatment of peri-anal abscess: It is not difficult to make the clinical diagnosis of perianal abscess. All patients with acute or chronic peri-anal condition must be thoroughly

evaluated and per rectum done routinely. Peri-anal abscess may extend depending on the

immunological status of the patient; therefore early treatment is mandatory to avoid thisand more serious morbidity. If patients require surgical incision, it should be done

promptly on first visit, or referral made if the surgery is unavailable. Otherwise,broadspectrum antibiotics such as amoxacillin-clavulanic acid (augmentin) alternativelyamoxacillin or ampicillin must be administered in sufficient dose for at least 10 days.

Palliative care including Sithz baths and analgesics are also important. Ultimately these

patients are enrolled in chronic HIV care.

2.4. Peri-anal and/or genital herpes:Latent or active infection with HSV I and II are common in the general population, and is

usually mild in immunocompetent persons. Severe cutaneous disease or visceralinvolvment is usually restricted to patients with advanced immunosuppression with a

CD4 count


24/109

Unit 3: Management of Opportunistic Diseases of the Nervous System

Neurological manifestations of HIV can occur at any time from viral acquisition to thelate stages of AIDS; they are varied and may affect any part of the nervous system

including the brain, spinal cord, autonomous nervous system and the peripheral nerves.

HIV affects the nervous system in 70-80% of infected patients. The effect may be due todirect effect of the virus, opportunistic infections and/or malignancies. For certainneurological manifestations a single aetiology is responsible while in others it is due to

multiple causes.

Most life-threatening neurological complications of HIV occur during the severeimmunodeficiency state and specific aetiological diagnosis in the Ethiopian setting is

often a major challenge. Thus, this unit attempts to guide the management of common

opportunistic infections and other treatable conditions in the nervous system

Diagnosis of neurological disorders in HIV in our setting depends on the history andstandard neurological examinations. In view of this, health care providers must be able to

perform a physical examination to detect neurological abnormalities. There can besingle or multiple abnormal neurological findings in the same patient necessitating

holistic neurological evaluation. Thus the examination should include assessment of:

Mental status comprising cognitive function, orientation and memory.

Cranial nerves

Motor function including DTR

Sensation

16


25/109

Table 6: Summary of common HIV-associated neurologicaland related syndromes

Syndrome Possibilities Diagnosis

Painful legs (extremities) Peripheral neuropathy,

metabolic disorders orvascular insufficiency.

Hx, Px, NCT

Difficulty walking Musculoskeletaldisorders, Spinal cord

lesions, Myopathies,

peripheral neuropathies,or some brain lesions.

Spinal X-ray,, CT, MRI,CK, LDH

LP when indicated

Severe headache +/focal neurological deficit

+/- seizure

Meningo encephalitis,Meningitis, CNS

Toxoplasmosis, brain

abscess, Tuberculoma,

CNS lymphoma.

Imaging (CT, MRI)LP when indicated

Acute confusion 1. Meningo-encephalitis

1 Systemicinfections like

malaria, or

septicaemia,2 Metabolic

disorders:

electrolyte

abnormalities,hypoglycemia,

renal or liver

failure

Blood film, CBC, blood

culture, LP (CSF

analysis)

RFT, LFT, RBS

electrolytes if diarrhoea

or dehydration present

Chronic behavioral

change

PML*

AIDS dementia,Chronic meningitis.

Clinical

CSF analysis

Always exclude local causes.*Has associated neurological deficits.

3.1. Peripheral Neuropathies

Peripheral neuropathies are among the most common causes of painful legs in HIVinfection; they arise as a complication of HIV infection itself, of drug therapy, or of other

metabolic or organ dysfunction or nutritional deficiencies.Distal symmetrical sensory polyneuropathy is the most common presentation but mono-

neuropathies can also occur. The neuropathies associated with HIV can be classified as:

17


26/109

Primary, HIV-associated

Secondary causes related to medications, OIs or organ dysfunctions

Diagnosis: Peripheral neuropathy diagnosis in HIV-infected patients is based on the

clinical picture presenting with pain, tingling sensations, paresthesia or numbness.Physical examination can reveal depressed or absent ankle reflex, decreased sensitivity todifferent modalities of sensation and in severe cases, difficulty in walking. The feet and

sometimes the hands are involved in symmetrical distribution. The diagnosis can be

supported by electro diagnostic studies including electromyography (EMG) and nerve

conduction studies (NCS) when available. Blood tests are frequently obtained to excludeother causes of neuropathy. In most instances, however, diagnosis is almost always

clinical.

Treatment

Avoid the offending agent if identified

Substitute or switch drugs such as d4T/DDI when the neuropathy is severe Remove other drugs associated with peripheral neuropathy

Supplement vitamin intake for all patients including concomitant administrationof pyridoxine with INH.

Adjuvants for pain management indicated for patients with pain and paresthesias

only.

Monitoring of events

Recognize presence of peripheral neuropathy

Asses severity at each clinical visit

Avoid drugs causing neuropathy

3.2. Persistent headache with (+/-) neurological manifestations +/- seizure

Headache is a very common symptom, found in diverse clinical conditions; whenpersistent and not improving with analgesics, it might indicate a serious underlying

condition particularly if accompanied by neurological abnormalities.

Approaches to management of persistent headache in HIV infection include:o exclude local causes e.g. sinusitis, dental abscess

o perform clinical assessment for presence of neurological signs or

symptomso look for evidence of meningismus or space occupying lesion

o if there is a sign of space occupying lesion look for papilloedema or focal

neurological deficit

o consider toxoplasmosis, brain abscess, tuberculoma, CNS lymphoma

o Perform lumbar puncture, if there are signs of meningitis; however deep

coma, recurrent seizure and hemiparesis with or without papilloedema arecontraindications to lumbar puncture.

18


27/109

3.3. Management of common CNS infections presenting with headacheand/or seizure

3.3.1 Toxoplasmosis

CNS toxoplasmosis is caused by the protozoan Toxoplasma gondii. In immunosuppressed individuals the disease occurs almost exclusively due to reactivation of latent

infection. Seroprevalence varies substantially in different communities; in Ethiopia,

general prevalence is about 80% in the adult population. Clinical disease is rare among

patients with CD4+

T lymphocyte counts >200 cells/L. The greatest risk is amongpatients with a CD4+ T lymphocyte count


28/109

First-line regimen in ideal circumstances:

Sulfadiazine, 1-2 gm p.o.q 6h for six weeks or 3 weeks after resolution of lesionS/E: crystal urea, rash

C/I: severe liver, renal and hematological disorders; known hypersensitivity to

SulfonamidesDosage/form: 500 mg tablets,

PLUSPyrimethamine

Loading dose of 200 mg once, followed by:Pyrimethamine 50-75 mg/day

S/E: rash, fever and bone marrow depression (neutropenia and thrombocytopenia)

C/I: folate deficiencyDosage/form: 25 mg tablets

PLUSFolinic acid (Leucovorin): 10-20 mg/d

S/E: allergyDosage/form: 5 and 10 mg tablets

OR

Pyrimethamine and Folinic Acid (Leucovorin): (standard dose)

PLUSClindamycin: 600 mg q 6 hrs

S/E: toxicities include fever, rash, and nausea, diarrhoea (including pseudomembranouscolitis or diarrhoea related to Clostridium difficile toxin)

ORPyrimethamine and Folinic acid (Leucovorin): (standard dose)

PLUS

Azithromycin: 900-1200 mg PO qd

However the 1st line regimen in the Ethiopian context is:

1. Sulfadoxine/pyrimethamine (Fansidar): 500 mg/ 25 mg po b.i.d for two days,followed by once daily both for four (4) weeks is given together with Folinic acid (10 mg

daily)

S/E: Occasional: anaemia- need Folinic AcidRare: pancytopenia; hepatitis; GI intolerance

C/I: Foliate deficiencyDosage forms: 500/ 25 mg tabs or IV vials

PLUSFolinic acid: 10-20 mg/d

2. The alternative regimen in Ethiopia is cotrimoxazole 15 mg /Kg

20


29/109

Trimethoprim in three divided doses daily when Fansidar cannot beadministered safely.

*Corticosteroids (dexamethasone 4mg PO or IV q6hrs) used if cerebral oedemapresent, discontinued as soon as clinically feasible. Corticosteroids might mask theevaluation of the clinical response particularly when therapy is initiated empirically.

3.3.2. Management of seizure associated with toxoplasmosis and other CNS OIsCNS toxoplasmosis or other CNS OIs can present with seizure activity which can be

focal or generalized. When such conditions occur, due attention should be given to

control the seizure on top of managing the underlying conditions.

Management of seizure or epilepsyApproach for patients with seizures or epilepsy

The seizure type(s) and epilepsy syndrome, aetiology, and co morbidity should bedetermined

All individuals with epilepsy should have a comprehensive care plan at primaryand secondary health care providers

The antiepileptic drug (AED) treatment strategy should be individualizedaccording to the seizure type, epilepsy syndrome, co-medication, co- morbidity,

lifestyle, and individual preference

All patients noted or suspected of having seizures should be seen urgently by a

care provider, for early diagnosis and initiation of therapy appropriate to theirneeds

Seizure is a common manifestation of toxoplasmosis and rarely crypto meningitis. Other

rare causes of seizure include mass lesions like lymphoma, metabolic disorders, systemicinfections or idiopathic causes. Seizure activity may be detected during jctal or post ictal

period and the management approach includes the following:

Ictal phase

Apply ABC of seizure

o secure airway and put gag in the mouth

o administer oxygen

o give 40% glucose and B1 when applicable

o draw blood for appropriate laboratory tests

o slowly administer Diazepam 5-10 mg possibly repeat dose according toneed and then Dilantinization

o refer or consult specialist while stabilizing or after ictal

period

Post-ictal phase Consider long term management

Start with phenytoin 100 mg t.i.d following Dilantinization orPhenobarbitone 100 to 200 mg / day can be given

Form long term treatment plan or refer to specialist

21


30/109

Monitoring Adverse Events

Changes in antibody titers are not useful for monitoring responses to therapy

Patients should be routinely monitored for adverse events and clinical and

radiological improvement. Common pyrimethamine toxicities include rash,

nausea, and bone-marrow suppression Laboratory monitoring to assess bone marrow depression to detect neutropenia,

anaemia, and thrombocytopenia that can often be reversed by increasing the

leucovorin to 50-100mg/day administered in divided doses

Common sulfadiazine toxicities include rash, fever, leukopenia, hepatitis, nausea,

vomiting, diarrhoea, and crystalluria. Common clindamycin toxicities includefever, rash, nausea, diarrhoea (including pseudo membranous colitis or diarrhoea

related to Clostridium difficile toxin), and hepatotoxicity. Common TMP-SMX

toxicities include rash, fever, leukopenia, thrombocytopenia, and hepatotoxicity.

Drug interactions between anticonvulsants and ARVs should be carefullyevaluated and doses adjusted according to established guidelines

Restart secondary prophylaxis if CD4 of patient with history of previous clinicaltoxo drops 200 cells/L on ART.Secondary prophylaxis should be resumed if the CD4+ T lymphocyte count

decreases to


31/109

3.3.3 Cryptococcosis

HIV-associated cryptococcal infections are caused by Cryptococcuss. Before the adventof ART, approximately 5-8% of HIV infected patients in developed countries acquired

disseminated cryptococcosis, but incidence declined substantially with the use ofeffective ART. The majority of cases are observed among patients with CD4+ T

lymphocyte counts of 200mm of water) in the majority of patients.

Disseminated disease is a common manifestation, with or without concurrent meningitis.Approximately half of patients with disseminated disease have evidence of pulmonary

involvement. Skin lesions might be observed.

Diagnosis depends on laboratory evidence of infection in the CSF. Indian ink staining ofCSF demonstrates the organism in up to 60% of cases. Cryptococcal antigen is almost

invariably detected in the CSF at high titer in patients with meningitis or

meningoencephalitis. Up to 75% of patients with HIV-1-associated cryptococcalmeningitis have positive blood cultures. The serum cryptococcal antigen is also usually

positive and detection of cryptococcal antigen in serum might be useful in initialdiagnosis. Deep coma, high opening pressure and/or high CRAG titer in the CSF often

indicate a poor prognosis.

Treatment Recommendations: Untreated cryptococcal meningitis is fatal.

First-line treatment: The recommended initial treatment for acute disease is

amphotericin B, usually combined with flucytosine, for 2 weeks, followed byfluconazole alone for 8 weeks.

Non-liposomal amphotericin B is the standard treatment during induction of cryptotreatment in the Ethiopian context. The dose is 0.1 mg/kg testing dose to be escalated to

0.6-1 mg/Kg for 2 weeks. Lipid formulations of amphotericin B appear effective and safe

but very expensive. The optimal dose of lipid formulations of amphotericin B is 4 mg/kg

body weight/daily.

23


32/109

After a 2-week period of successful induction therapy, consolidation therapy should be

initiated with fluconazole administered for 8 weeks or until CSF cultures are sterile.

Alternative treatment: Therapy with fluconazole alone at a dose of 400-800 mg/daily iseffective for treating AIDS-associated cryptococcal meningitis.

Increased intracranial pressure might cause clinical deterioration despite a microbiologic

response, probably reflects cerebral oedema, and is more likely if the CSF openingpressure is >200mm H2O. The opening pressure should always be measured when a

lumbar puncture is performed.

The principal initial intervention for reducing symptomatic intracranial pressure isrepeated daily lumbar punctures. CSF shunting should be considered for patients in

whom daily lumbar punctures are no longer tolerated or signs and symptoms of cerebral

oedema are not relieved.

*Corticosteroids (Dexamethazone) Unlike with other situations of intracranialpressure, these drugs have no beneficial effect.

Seizure activity associated with Cryptococcus meningioencephalitisSee CNS toxoplasmosis associated seizure

Monitoring Adverse Events

Infusion of test dose (0.1mg/kg) before initiation of Amphotericin standard dose

is important to avoid anaphylactic reaction

A repeat lumbar puncture to ensure clearance of the organism is not required for

those with cryptococcal meningitis and improvement in clinical signs andsymptoms after initiation of treatment. If new symptoms or clinical findings occur

after two weeks of treatment, a repeat lumbar puncture should be performed.

Serial measurement of CSF cryptococcal antigen or culture or Indian ink staining

might be more useful but requires repeated lumbar punctures and is not routinely

recommended for monitoring response.

Patients treated with amphotericin B should be monitored for dose-dependentnephrotoxicity and electrolyte disturbances. Infusion-related adverse reactions

(e.g., fever, chills, renal tubular acidosis, hypokalemia, orthostatic hypotension,

tachycardia, nausea, headache, vomiting, anaemia, anorexia, and phlebitis) mightbe ameliorated by pre-treatment with acetaminophen, diphenhydramine, or

corticosteroids administered approximately 30minutes before the infusion. Lipidformulations of amphotericin B are less toxic.

Prevention of Recurrence

Secondary prevention: Patients who have completed initial therapy for cryptococcosisshould be administered lifelong suppressive treatment (i.e. secondary prophylaxis or

24


33/109

chronic maintenance therapy), unless immune reconstitution occurs as a consequence ofART.

Secondary prevention can be discontinued when CD4 remains above 200/dl for 3-6

months.

Adult and adolescent patients appear at low risk for recurrence of cryptococcosis when

they have successfully completed a course of initial therapy, remain asymptomaticregarding cryptococcosis, and have a sustained increase (i.e. >6 months) in their CD4+ T

lymphocyte counts to >100-200 cells/L after ART. On the basis of these observations

and inference from more extensive data regarding safety of discontinuing secondaryprophylaxis for other opportunistic infections during advanced HIV-1 disease,

discontinuing chronic maintenance therapy among such patients is a reasonableconsideration.

Maintenance therapy should be re-initiated if the CD4+ T lymphocyte count decreases to


34/109

As noted above, diagnosis of CNS TB can be difficult. Maintaining a high degree ofsuspicion is vital in order to initiate therapy promptly. The proper examination of CSF

specimens is of critical importance to early diagnosis. Typically, the CSF formula shows

elevated protein and lowered glucose concentrations with a mononuclear pleocytosis.CSF protein ranges from 100- 500 mg/dL in most patients. The CSF glucose is less than

45 mg/dL in 80% of cases. The usual CSF cell count is between 100 and 500 cells/L.

Treatment: Specific antituberculous chemotherapy should be initiated on the basis ofstrong clinical suspicion and should not be delayed until proof of infection is obtained.

The clinical outcome depends greatly on the stage at which therapy is initiated; much

more harm results from delay, even for only a few days, than from inappropriate therapyas long as efforts are continued to confirm the diagnosis.

All patients should initially receive a combination regimen of isoniazid (INH), rifampin,

pyrazinamide (PZA), and ethambutol (EMB) as category I. The recommended regimen isa four drug combination that includes INH, rifampin, PZA, and EMB for two months

followed by INH and rifampin/ETM for 10 months. There is evidence to recommend

adjunctive corticosteroid therapy both adults and children with tuberculous meningitis.Recommended regimens:

Prednisone 60 mg per day tapered gradually over six weeks or

Dexamethasone intravenously for the first three weeks (initially 0.4 mg/kg perday, tapering to 0.1 mg/kg per day), followed by oral administration beginning

4mg per day, tapered over three to four weeks at the rate of 1 mg decrease in thedaily dose each week

Unit 4: Management of Skin Disorders

The skin is an organ frequently affected by OIs; early manifestations of HIV infections

frequently occur in the skin. Different kinds of OIs, such as herpes zoster, and other viral,fungal and bacterial infections occur in the skin. Manifestations of adverse drug reactionsand non-infectious conditions also occur in the skin. Some skin reactions to drugs such as

Nevirapine may be life-threatening. In most instances diagnoses of skin disorders with

HIV disease are made on clinical grounds. Most skin disorders in HIV disease can becured or ameliorated, but a few fail to improve even with good general clinical and

immunological responses to ART.

Pruritis is the most common dermatologic symptom in HIV infected patients. It can belocalized indicating primary skin lesion, or generalized that may or may not indicate

primary skin lesions. In many patients pruritus may be severe and not amenable to

available therapy. The most common skin conditions associated with pruritis in patients

with AIDS include the following:1. excessive dryness of the skin ( Xerosis cutis)

2. eczemas like seborrheic dermatitis or contact dermatitis

3. folliculitis that may include infections by Staphylococcus aureas orhypersensitivity to insects

4. drug eruptions

5. scabies6. intertrigo ( candida, tinea, herpes simplex)

26


35/109

In most patients, diagnosis can be established by examining the lesions. However, as

immune deficiency advances it may be useful to use investigations such as biopsy to

diagnose specific dermatosis or use staining and culture to diagnose specific infections.

4.1 Aetiological Classification of Skin Disorders in HIV Disease.

Skin disorders in HIV infected patients can occur due to infections, neoplasm, and

hypersensitivity to foreign agents including drugs, or to unknown causes. Nevertheless,

infections are commonly seen in clinical practice; refer to the following table:

Table 7: Aetiological Classification of Skin Disorders in HIV Disease

Infections Disease Clinical presentations Treatment RemarkBacterial Cellulitis Poorly defined erythema.

Pus and crust at the site

plus signs of

inflammation

Amoxicillin

500mg tid for

ten days or

erythromycin

500mg qid if

allergic to

penicillin.

Mostly

encountered in

lower

extremities

and often

unilateral.

Impetigo Erythematous small

papules usually limited to

few lesions coalescing in

to crusted plaques.

Use topical

antibiotic; use

amoxicillin for

extensive

disease.

Usually a

superficial

lesion

Carbuncle Nodular lesion with

extensions to the deeper

structure. Signs of

inflammation present.

Use cloxacillin

500 mg qid for

ten days.

Involves the

trunk as well

as extremities.

Viral Herpes simplex Painful vesicular lesion

around mouth or

genitalia. Recurrent and

extensive; difficult to

eradicate during

advanced immune

deficiency

Acyclovir 400

mg tid for ten

days.

If chronic (>

one month)

indicates

eligibility for

ART.

Herpes zoster Painful and vesicular

eruptions with

dermatomal distribution.

When healed, scar will

remain.

Acyclovir 800

mg 5 X per day

for seven days.

Monitor renal

function.

When it

involves the

eyes it is a

medical

emergency.

Do not give

acyclovir if

duration is >72

hours.

Warts/veruccae Painless flat to raised

warts over fingers or

genitalia. In advanced

Podophyllin

Imiquimod

Cryotherapy

premalignant

and risk for

cervical cancer

27


36/109

immune deficiency, they

tend to be multiple and

exophytic.

Consult

experts.

Molluscum

contagiosum

Umbilicated and raised

facial lesions that tend to

be very big during

immune deficiency state.

May not

require therapy;

HAART if

eligible

Contagious

Parasitic

infestation

Scabies Pruritic lesions ranging

from pinpointed

erythematous papules

involving interdigital and

gluteal places to varying

degrees of hyperkeratotic

plaques associated with

significant skin

thickening and crusting.

BBL, lindane

or permethrin

to be applied to

whole body.

Ivermectin 200

microgram/kg

stat orally.

Burrows are

visible in mild

infestations

but in crusted

scabies may

not be evident

leading to

misdiagnosis.

Fungus Dermatophytosis Superficial causing

ringworm or athletes

foot.

Topical antifungal for limited

skin affected.

Fluconazole for extensive lesions100mg daily for ten days.

Thrush White plaques on the

buccal mucosa including

the tongue that can be

scraped off leaving red

base. Can be associated

with candida paronychia

or intertrigo.

Miconazole gel 2% apply bid

Fluconazole 100 mg daily for ten

days for recurrent or

oropharyngeal thrush.

Deep fungal

infection

Presentation varies from

fungating nodules and

tumors to ulcers and

diffuse papulonodulardisease

Disseminated Cryptococcus can

be confused for molluscum

contagiosum.

Treat with amphotericininduction and/or fluconazole

maintenance.

4.2. Selected skin conditions in patients with HIV infection

4.2.1 Seborrheic Dermatitis: Seborrheic dermatitis is often associated with HIVinfection and the extent of disease is inversely correlated with patients CD4 level. Itpresents with greasy and erythematous scales localized to nasolabial folds, ears and scalp.

Treat with topical steroids and antifungal agents; e.g. candicort cream to be applied on

the lesions bid and ketoconazole cream or shampoo for the scalp.

Adverse Drug Reactions: Adverse drug reactions involving skin are common amongHIV infected patients because of the large number of medications they require and

the underlying altered immune status. Clinical manifestation ranges from simplemorbilliform eruptions with erythematous macules and papules to life-threatening

bullous eruptions or palpable purpura. Systemic symptoms like fever, rigors and

intolerable pruritis often indicate severity of the reaction. Management includesdiscontinuation of the offending drug if the reaction is severe, or desensitization for

28


37/109

mild reactions, if treatment with the offending drug is absolutely necessary; e.g.cotrimoxazole treatment for PCP. Do not continue offending drug if the reaction is

severe with wet lesions (blisters) and/or is accompanied by systemic symptoms like

fever and when mucus membranes are involved. Commonly-used drugs associatedwith ADR involving the skin include;

1. Sulphonamide drugs ( fansidar and cotrimoxazole)2. anti TBC drugs ( rifampin, INH and thiacethazone)

3. NNRTI ( nevirapine and efavirenz)

4. NRTI (abacavir)

5. Penicillin6. Anticonvulsants (carbamazepine and phenytoin).

4.2.2 Pruritic Papular Eruption

Pruritic papular eruption is common among HIV infected patients causing substantial

morbidity in sub-Saharan Africa. Its prevalence ranges from 12-46% and it isuncommon in HIV negative patients (PPV of 82-87%, and may play role in

diagnosing HIV). The pathogenesis is unknown but it may be related to

hypersensitivity to arthropod bites. In extreme form, eosinophilia and eosinophilic

infiltrates of the skin are present. Severity of rash often correlates with CD4 count.

The clinical manifestation is intensely pruritic, discrete, firm papules with variable

stages of development and predilection for extremities, though they can involve trunkand face. Excoriation results in pigmentation, scarring and nodules. Treat with topical

steroid and oral antihistamines; however it is often refractory to treatment and henceshort course prednisolone may be used. HAART is often effective.

4.2.3 Kaposis Sarcoma

This is a tumour caused by human HSV type 8 viruses. It was common in North America

before the advent of ART but the incidence of KS in HIV-infected individuals isincreasing in sub-Saharan Africa, where there is limited access to ART. In fact, AIDS-

related KS has become the most frequently diagnosed tumour in several African countries

though rarely seen in Ethiopia. The clinical features of KS are described below.

Skin lesions: KS usually manifests dermatologically as pigmented macules, plaques,papules, or nodules, commonly involving the tip of the nose. They range from a fewmillimetres to large confluent areas several centimetres across. Usually KS lesions look

purple but in dark-skinned people appear dark brown or black.

Lesions of the oral cavity occur in about one third of patients with AIDS-associated KS.Hard palate lesions are most common. These flat, red or purple plaques, either focal or

diffuse, may be completely asymptomatic and easily overlooked. In other patients,

however, larger nodular lesions involving the hard or soft palate, or both, may become

exophytic and ulcerated, and may bleed. Other oral sites of KS involvement include the

29


38/109

gingiva, tongue, uvula, tonsils, pharynx, and trachea. These lesions may interfere with

eating and speaking, cause tooth loss, or compromise airway.

Gastrointestinal KS may occur throughout the GI tract, and although most patients areasymptomatic, some experience pain, obstruction, or bleeding. Digital examination may

reveal rectal KS, but diagnosis generally requires endoscopy. Most lesions are submucosal and readily visible on contrast-enhanced radiographs.

Other sites of KS include the lungs, lymph nodes, many visceral organs, including liver,spleen, heart, pericardium, bone, and bone marrow.

Poor prognostic indicators include a disseminated tumour with CD4 count below 200/Land/or presence of systemic symptoms like fever, weight loss and sweating.

Treatment of KS depends on extent of tumour spread. Localized lesions could resolve

with ART alone. Disseminated or locally aggressive tumours require radiation therapy orchemotherapy in addition to ART and hence require referral to centres with this expertise.

Unit 5: Management of Fever.

Fever is a common result of opportunistic infections in patients infected with HIV.

However causes of febrile illnesses in the general population can also be responsible.Unexplained fever occurs frequently in HIV-infected patients and in most patients with

advanced immune deficiency. The purpose of this unit is to understand common

aetiologies of fever among patients infected with HIV and principles of its management.

Definition of Fever:

Fever is defined as elevation of body temperature >37.2C in the morning or

>38C after 4 p.m. in the afternoon. Take temperature orally as axillaryreadings are often unreliable.

Unexplained chronic fever (>one month) is suggestive of advanced immunedeficiency state. This scenario is called Fever of Unknown Origin and isdefined as fever >38C lasting more than four weeks as an outpatient or four

days following patient admission and remains unexplained despite exhaustive

clinical and laboratory evaluation.

Aetiology: Causes of fever in HIV-infected patients can be identical to those in thegeneral population. These include malaria, typhoid fever, typhus, relapsing fever, measles

and meningitis. However, unexplained fever in HIV-infected patients often signifiesadvanced immune deficiency. Opportunistic infections are responsible for unexplained

fever and of these; tuberculosis is the most common in patients with very low CD4 count.

Consequently, empirical treatment for TB is recommended when blood culture forMycobacterium tuberculosis is unavailable and other causes are ruled out. One should not

start Isoniazid Preventive Therapy (IPT) and it is advisable to delay ART until the cause

of fever is identified; otherwise IRIS will be a serious complication shortly after initiation

of ART.

30


39/109

1

23

4

56

OIs presenting with unexplained fever in HIV-infected patients.

. Bacterial infections: Salmonella species, Pneumococcal bacteraemia.

. Fungal infections: Pneumocystis jiroveci, Cryptococcus.. Mycobacterium infections:M. tuberculosis, MAC

. Protozoa infection: Leishmania donovani.

. Viral infections: CMV

. Non infectious disorders: lymphoma

Diagnosis: The clinical history should elaborate onset, duration, pattern, severity,accompanying symptoms and related complaints. Travel history to areas endemic formalaria and Kala-azar is essential. History of exposure to animals can indicate source of

fever in some patients. Inquire about drug intake as medication could be the cause.

Perform systematic meticulous physical examination. Focus on HEENT, intercostal areasand the precordium to elicit tenderness or abnormal findings

Do not omit a pelvic examination in women because pelvic abscess is a

recognized cause of chronic fever. Similarly, rectal examination can revealperianal abscess, which could explain fever. Examination of fundi by

ophthalmoscope is useful to see retinal changes or papilloedema

The epidemiology of febrile illnesses and clinical onset of symptoms should

direct types of investigations required.

Treatment: Management of fever includes supportive care, palliative care and treatmentof underlying cause. Supportive care includes correction of fluid and electrolyte deficit;

and because fever enhances catabolism, offer adequate nutritional supplement. The fevershould come down to normal using antipyretics such as a standing dose of paracetamol.

Avoid aspirin as it may cause stomach irritation. Fanning and cold compression areadjuvant treatment modalities whenever fever is difficult to control with paracetamol.

Definitive treatment of the cause depends on isolation/detection of the organismresponsible. The following table should guide treatment.

31


40/109

Table 8: Summary of febrile syndromes in Ethiopia

Disease * Clinicalpresentation

Investigation RecommendedTreatment

Remarks

Malaria Acute onset of

fever, chills,

headache,

hepatosplenomegaly

Thick and thin

blood film

Coartem for

uncomplicated

falciparum malaria;

Quinine for

complicated falciparum

malaria; Chloroquine

for vivax malaria.

Severe manifestations

(severe anaemia, altered

mental state, hypotension,

renal impairment, bleeding

tendency, hypoglycaemia in

pregnancy) should warrant

admission. PI and NNRTI

can reduce serum level of

Coartem

Relapsing

fever

Acute onset of

fever, chills,

headaches ,

epistaxis,

hepatosplenomegaly

Blood film Admit patient, establish

IV line

Procaine penicillin

400,000 units IM

followed by

doxycycline 100mgorally next day.

Observe for Jarish-

Herxheimer reaction and

manage by fluid

replacement with normal

saline solution. Digitalize if

indicated.Delouse scalp, hair and

clothes.

Typhus Acute onset of

fever, chills,

headache ,

epistaxis,

hepatosplenomegaly

; severe prostration

if louse born

High titer of

Weil-Felix

serology with

clinical setting

where patient

has body louse

or exposure to

rat flea.

Doxycycline 100mg

bid for seven days.

Chloramphenicole

500mg qid for seven

days.

Delouse scalp hair and

clothes.

Observe for complications

such as renal impairment

and stroke.

Typhoid

fever.

Acute onset of fever

chills, headache,

epistaxis,hepatosplenomegaly

, often diarrhoea.

Positive blood

culture

Four-fold rise intiter of anti body

against somatic

antigen of Widal

test

Ciprofloxacin 500mg

bid for seven days

Check for renal function and

substitute chloramphenicole

if impaired.

Leishma

niasis

Chronic fever,

cachexia, anaemia,

hepatosplenomegall

y and patient from

endemic `area.

Spleen aspirate

show amastigote

on Wright or

Giemsa stain

DAT for

presumptive

diagnosis

SSG(pentostam

20mg/kg daily IM for

28 days

Liposomal

Amphotericin B or

Miltefosine for resistant

cases

Recurrence and drug

interaction with ART can

create problem.

MAC Chronic fever,

anaemia, cough,hepatosplenomegaly

, hepatitis and

diarrhoea.

Culture of

atypicalmycobacteria

from sputum or

blood.

CD4 two weeks

- Other constitutional symptoms e.g. weight loss, fever,

- Chest X-ray suggestive of lung tuberculosis

Any patient with suspected TB should be assessed with three sputum smears

and chest X-ray, and be offered HIV testing if status is unknown or reasonabletime has elapsed since the last negative test result.

The major issues in the clinical management of patients co-infected with HIVand active TB are: when to start ART, possibility of high pill burden, risk of

drug interactions, drug toxicity, and IRIS. However, in HIV-infected patientswho present with TB, priority must be given to initiate DOTS.

63


72/109

8.1 In co-managing TB-HIV there are two scenarios to consider:

A. Patient developing TB while on antiretroviral therapy:

A.1. If a newly-initiated ART patient (i.e. treatment naive patient) develops TB withinthe first 3-6 months after treatment, proceed as follows:

Start DOT without delay, per national recommendation;

If the patient is on nevirapine, substitute it with EFV when possible, whilepatient is on Rifampicin. If this is not possible (e.g. due to intolerance or

other major efavirenz related side effects or significant risk of pregnancy),

use triple nucleoside analogues, i.e., ABC/3TC/ZDV. Other than changingnevirapine to efavirenz, continue with the same nucleoside/nucleotide

backbone.

Start CP.

A.2 If a patient develops active TB after more than six months of ART, the possibility oftreatment failure should be considered when diagnosis is extra-pulmonary

tuberculosis and there are concomitant diseases suggesting advanced immunedeficiency. If treatment failure is established, the patient should be managed with an

appropriate second-line regimen decided by an experienced physician. This must be

started as soon as the patient tolerates the anti TB drugs. Since PIs are usually used

in 2nd

line regimens, delaying the initiation of the 2nd

line until completion of heintensive phase is better since refabutine is not available. It is also recommended to

do a liver function test every two weeks for at least eight weeks to determine the risk

of added hepatic toxicity. In the absence of evidence for ARV treatment failure, thepatient should be managed per A.1.

8.2. Patient on anti-TB or newly-diagnosed active TB:

If an HIV-infected patient not on ART presents with TB, the first priority istreating the TB per the national TB-treatment guidelines. As TB treatment

requires a relatively long period, the issue is decision with regard to eligibility and

timing of ARV initiation:

64


73/109

Table 10: Guide for management of patients presenting with TB beforeinitiation of ART

Recommendation Preferred ARV regimen

CD4 count

250 use EF

In pregnant women with CD4 >250 use triple NRT

containing ABC/3TC/ZDV

Start EFV containing regimen if the continuation

phase includes rifampicin

CD4

>350/mm3 Start TB treatment

Defer ART

Re-assess eligibility for ART at 24 weeks clinicall

and immunologically, in the course of TB-

treatment, at completion of TB treatment, or as

indicated.

CD4 not

available Start TB treatment.

Start ART after 2-8 weeks TB

treatment if patient has severe

disease and/or other clinical

indicators of advanced immune

deficiency

Start ART after completion of

intensive phase when patient is

not seriously ill or other signs of

advanced immune deficiency are

absent

.

Start NVP containing regimen if the continuation

phase does not include rifampicin.

If a non-pregnant woman has CD4 of >250 use EF

In pregnant women with CD4 >250 use triple NRT

containing ABC/3TC/ZDV

Start EFV containing regimen if the continuationphase includes rifampicin

1 Timing of ART initiation should be up to clinical judgment based on other signs of immunodeficiency indicating progression of HIVdisease (Refer to Table 1). For TB patients in WHO clinical Stage IV, ART should be started as soon as TB treatment is toleratedirrespective of CD4 count.

2 EFV containing regimens include d4T/3TC/EFV or ZDV/3TC/EFV.3 NVP (200 mg daily for 2 weeks followed by 200 mg twice daily) may be used in place of EFV in absence of other options. NVP

containing regimens include: d4T/3TC/NVP or ZDV/3TC/NVP.5 Start ART if non-TB Stage IV conditions are present

65


74/109

Patient on ART develops active TB

Patient develops TB following 3-6 months of ARV therapy:

Initiate DOT per the national guidelines

Continue ARV therapy throughout TB treatment

Patients on first-line therapy containing nevirapine should be changed toefavirenz as follows:

Stavudine 30mg or Zidovudine (AZT) 300 mg every 12 hours+

Lamivudine 150mg every 12 hours+Efavirenz 600mg at night

If EFV is not available or there are problems with EFV, use triplenucleoside containing ABC, if patient develops ABC hypersensitivitycontinue with NVP and monitor liver function every month.

Table 11: shared side effects of anti-TB and ARV drugs

Side effects ARV drugs Anti-TB drugs

Nausea ZDV, RTV, ddI Pyrazinamide

Hepatitis NVP, EFV Rifampicin, INH, Pyrazinamide

Peripheral neuropathy d4T, ddI INH

Rash NVP, EFV Rifampicin, INH, Pyrazinamide

66


75/109

Remember:

Patients on TB medication and antiretroviral drugs also probably take cotrimoxazole for

prophylaxis, and therefore are on a large number of pills. Besides the pill burden, theymight also experience side effects of the different drugs, and remembering the different

dosages might also be difficult. Therefore, do pre-emptive counselling, provide support

and continue education to improve treatment adherence.

Patients should be routinely communicated with, counselled and educated about:When ART is started, TB symptoms may transiently worsen due to IRIS.

HIV-positive persons should be routinely screened for TB at enrolment, and during each

follow-up visit. The national TB/HIV guidelines recommend administration of INHPreventive Therapy (IPT) to HIV-infected persons after exclusion of active TB. Refer to

the TB-HIV national guidelines for eligibility criteria to initiate IPT.

9. HIV-Hepatitis Co-infection

Hepatitis B is endemic in many resource-limited countries, including Ethiopia.

Since transmission of HBV follows the same model as HIV, the co-infection rateis also high. Hepatitis C virus infection occurs predominantly in injected drug

users. HCV/HIV co-infection also occurs among this subset of the population.

HIV influences the natural course of HBV: a higher rate of progression to

advanced liver disease occurs in patients with HIV/HBV co-infection.

Tests for HBV infection markers such as HBsAg are limited to a few hospitalsand private laboratories in Ethiopia. The usual scenario in the care of HIV-infected cases in resource-limited settings is elevated transaminases. In such

situations EFV is preferred to NVP, particularly when the transaminase level is

above four times the upper limits of normal.

Patients started on ART may develop mild or severe HBV related IRIS. Mildercases present with some elevation of transaminases. In such situations, continue

ART. However, sort out the reason for liver disorder may be difficult because of

limitations of lab capacities in most treatment centres in Ethiopia, thus there ishigh chance of discontinuing ART.

ARV drugs such as 3TC and TDF are useful for treatment of HBV. 3TC is used

as first-line drug in almost all ARV regimens; whether a patient has HBVinfection or not. In order to select TDF for both HIV and HBV treatment, at least

HBsAg must be determined. However, the preferred first line regimen in thisguidelines is TDF/FTC/EFV, therefore, there is no need to do HBsAG to put

patients on TDF based regimen now.

Patients who have been on ARV regimens containing 3TC with or without TDF

may develop flare up of HBV when treatment is discontinued.

67


76/109

10. Use of ARV in women of child-bearing potential or pregnancy

Clinical staging is the same for a pregnant or postpartum woman as for any adult.

Use the same staging criteria. The only modification is the weight loss criteria in

clinical stage 2 and 3. For a pregnant woman, failure to gain weight during

pregnancy can be considered the same as weight loss.

The guiding principle for ARV use in women of childbearing age or pregnant

women is that the therapeutic decision is based solely on their need and eligibilityfor ART as outlined in section 4.1.

In situations of resource shortages priority should be given to CD4 testing forpregnant women. If CD4 testing is available but limited, priority should be given

for pregnant women in stage 1, 2 or 3, in order to decide whether to start ART orto give ARV prophylaxis.

A pregnant woman who came primarily for antenatal care and tested HIV-positive

can be upset by the test result and might not want to think about ART. It isimportant to counsel her on the advantages and the urgency of PMTCTinterventions, about accessing HIV care and treatment to maintain her health.

Pregnancy does not preclude the use of ART. However, considerations related to

pregnancy may affect the choice of antiretroviral regimen.

EFV is not recommended for use in women in their first trimester of pregnancydue to its potential for teratogenic effect on the foetus. EFV is not also

recommended for women with childbearing potential without provision of

effective contraceptive.

The combination of the dual NRTIs, d4T and ddI should be avoided duringpregnancy due to the high risk of toxicity (e.g. Lactic acidosis).

Make sure HIV-positive pregnant woman are offered the appropriate option:

1. ART when the woman is medically eligible plus ARV prophylaxis to thenewborn

OR

2. ARV prophylaxis both for the mother and the newborn when the woman isnot yet eligible for ART.

68


77/109

There are three clinical scenarios for ARV drugs use during pregnancy:

10.1 Women who become pregnant while on ART:

Women who become pregnant on d4T/3TC/NVP regimen should continue withthe same regimen throughout pregnancy, and thereafter. ALT should be

performed as indicated.

For women on EFV and in first trimester, as soon as pregnancy is suspected orconfirmed, the EFV should be replaced by nevirapine and the other drugs should

be continued. In case the pregnant mother has CD4 >250, triple NRTI are

preferred (ABC, 3TC, ZDV)

Women who develop severe pregnancy-related nausea and vomiting (hyperemesisgravidarum) might require temporary discontinuation of treatment. When this is

indicated, all drugs should be stopped and restarted at the same time. Treatment

should be restarted after all symptoms of hyperemesis have subsided to ensure thedrugs will be well tolerated

Triple therapy (HAART) is most effective to reduce mother-to-child transmissionof HIV. However, the neonate should be offered ARV prophylaxis as per the

recommendation of national guidelines for exposed neonates

10.2 Pregnant women eligible for ART

ART during pregnancy, when medically indicated, will improve the health of the

woman and is most effective in decreasing the risk of transmission of HIV to theinfant

If ART is indicated, delay the initiation until 12 weeks (i.e. end of first trimester)unless the benefit of early treatment outweighs any potential for teratogenicity;

e.g. mother has evidence for advanced HIV infection (i.e. clinical stage 3 or 4,

CD4 under 200 in any clinical stage)

In women eligible for ART, the benefit of early therapy clearly outweighs anypotential foetal risks and thus therapy should be initiated

HIV-infected women should be assessed for OIs and ART eligibility as part of

routine maternal care; anaemia should also be routinely checked for bymeasuring haemoglobin on the first and follow up visits

Start ART after the first trimester, with AZT containing regimen (i.e.AZT+3TC+NVP). In patients with moderate to severe anaemia d4T+3TC+NVP

69


78/109

can be used alternatively and the anaemia should be treated at the same time. Inpregnant women with CD4 >250 cells/microliter use EFV. If there is

contraindication to EFV consider triple NRTI (ABC/3TC/ZDV)

10.3 Pregnant women not eligible for ART: HIV-positive pregnant women not eligible for ART should receive ARV

prophylaxis for PMTCT purposes, as per the national PMTCT guidelines.

In all the three clinical scenarios for the use of ARVs in pregnant mothers, ARV

prophylaxis should be administered to the newborn, based on thenational PMTCT guidelines

10.4 Monitoring therapy during antenatal care

A pregnant woman needs determination of haemoglobin before and then at 4, 6

and 12 weeks after starting AZT. Because of the haemo dilution that occursnormally in pregnancy, severe anaemia is defined as less than 7 g/L

If ART is provided in the antenatal clinic, the mother should return for weeklyvisits at least four times, then resume twice-weekly visits until 38 weeks

gestation, when weekly visits should resume

At each follow-up visit, providers should assess adherence to treatment,occurrence of any new signs and symptoms including adverse reactions to theARV drugs, pregnancy-related problems or complications, IRIS or any other

conditions (e.g. malaria)

Routine lab testing should follow established national ANC guidelines

Encourage institutional delivery, partner testing and testing of other children

Inform/counsel the mother that treatment should continue through labour,delivery, postpartum period, and thereafter

An HIV-positive pregnant woman needs extra post-test counselling and support:

She needs counselling to understand the benefits and accept taking either ARV

prophylaxis or ART. Both prevent MTCT; and ART protects her health also

She needs support to disclose her HIV status to her partner and to get her partner

tested. Disclosure may not be simple, however, on-going counselling and

understanding the problems of the pregnant and nursing mother are very important.

Lack of disclosure is very much related with poor adherence to clinical and drugadherence.

Extra support is needed if she is medically eligible for ART. Adherence preparation

and initiation of ART might need to be rapid to ensure maximum benefit from ARTto prevent MTCT

HIV-positive women might suffer additional stigma and discrimination when they

are pregnant, and they themselves might feel guilty about giving HIV to their baby.This feeling of guilt may in turn affect her ability to adhere to ART. It is important

to address the guilt and assist her in getting beyond it.

70


79/109


80/109

72

Managing HIV-infected Pregnant Women

All HIV-infected women should routinely be assessed for presence of OIs, including TB,and eligibility for ART during pregnancy, delivery and postnatal checkups. With regard to

eligibility to ART, there are three scenarios:

1. Pregnant women not eligible for ART:

Manage per the national MCH and PMTCT guidelines.

Follow clinically and immunologically (every 3 to 6 months by CD4 count) to decide on

initiation of ART.

2. Pregnant women who are eligible for ART:

Commence on first-line treatment:

AZT 300 mg every 12 hrs3TC 150 mg every 12 hrs

NVP 200 mg daily for 2 weeks, then 200mg every 12 hrs

ORUse d4T if the Hgb level is 250, history of toxicity, on DOTS intensive

phase) put on triple NRTI including ABC/3TC/ZDV. If patients are in the 2nd or 3rd trimester

EFV based regimen may be given (TDFor ZDV/FTC or 3TC/EFV) Such patients require

attention of ART experienced physicians; therefore they require referral to facilities where

these are available.

All infants born to HIV-infected women should receive a course of ARV drugs as post-exposure prophylaxis, per the national PMTCT guidelines


81/109

Fixed Dose Combination

or Single ARVs

Dosage Side-Effects Interactions

Triple ART FDCs

TDF+FTC+EFV

300mg TDF+ 200mgFTC+600mg EFV

One tablet daily

CNS toxicityTeratogenicity in the firsttrimester pregnancy

Rarely renal insufficiency

Avoid during firsttrimester pregnancyAvoid fatty meal

D4T+3TC+NVP

30 mg d4T+ 150 mg 3TC+ 200mg NVP

One pill twice daily after initial 2weeks of NVP given as single200 mg tablet daily

Skin Rash, Hepato-toxicity,

pancreatitisPeripheral Neuropathy

Lactic acidosis/ fatty liverLipoatrophy

Avoid:

NVP with RifampinD4T with ddI

D4T with AZT

guia para diagnostico de vih

Documents